Reviewed, UniProtKB/Swiss-Prot P51797 (CLCN6_HUMAN)

Names and origin

Protein names

Recommended name:
    Chloride channel protein 6
      Short name=ClC-6

Gene names

Name:	CLCN6
Synonyms:	KIAA0046

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	869 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Testis, ovary, small intestine, brain and skeletal muscle. Low level expression in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Isoform C is only detected in kidney.
Sequence similarities	Belongs to the chloride channel (TC 2.A.49) family. [View classification] Contains 2 CBS domains.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	CBS domain Repeat Transmembrane
Ligand	Chloride
Molecular function	Chloride channel Ionic channel Voltage-gated channel
Gene Ontology (GO)
Biological process	cell volume homeostasis Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB chloride transport Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB signal transduction Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB
Molecular function	chloride ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated chloride channel activity Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P51797-1)

Also known as: Clc-6a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: P51797-2)

Also known as: ClC-6b; D2-A1;

The sequence of this isoform differs from the canonical sequence as follows:
     237-320: DKRDFVSAGA...LLNFGEFKCS → YGKRQERLCI...APWIAELWRV
     321-869: Missing.

Isoform C (identifier: P51797-3)

Also known as: ClC-6c; D1-A1;

The sequence of this isoform differs from the canonical sequence as follows:
     319-353: CSDSDKKCHLWTAMDLGFFVVMGVIGGLLGATFNC → SLREPPCVSGNHRGGVCGLDGVRRMPTDVLFESNR
     354-869: Missing.

Isoform D (identifier: P51797-4)

Also known as: ClC-6d; D1-A2;

The sequence of this isoform differs from the canonical sequence as follows:
     237-308: DKRDFVSAGA...QFGSWGSFQL → SGCWSCCSFR...APWIAELWRV
     309-869: Missing.

Isoform E (identifier: P51797-5)

The sequence of this isoform differs from the canonical sequence as follows:
     844-869: IVGIITRHNLTYEFLQARLRQHYQTI → VSEAPALPPP...LHLRRDLRIR

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 869	869	Chloride channel protein 6		PRO_0000094449
Regions
	Transmembrane	82 – 102	21	Potential
	Transmembrane	130 – 150	21	Potential
	Transmembrane	184 – 204	21	Potential
	Transmembrane	245 – 265	21	Potential
	Transmembrane	334 – 354	21	Potential
	Transmembrane	375 – 395	21	Potential
	Transmembrane	462 – 482	21	Potential
	Transmembrane	511 – 531	21	Potential
	Domain	605 – 662	58	CBS 1
	Domain	807 – 868	62	CBS 2
	Compositional bias	4 – 18	15	Cys-rich
Natural variations
	Alternative sequence	237 – 320	84	DKRDF…EFKCS → YGKRQERLCISRSGCWSCCS FRGANRGYLVQSRGGFVLLE PRAHVESALLFHVCHLHPQL LPFWDSVWKLGFLPAPWIAE LWRV in isoform B.		VSP_001043
	Alternative sequence	237 – 308	72	DKRDF…GSFQL → SGCWSCCSFRGANRGYLVQS RGGFVLLEPRAHVESALLFH VCHLHPQLLPFWDSVWKLGF LPAPWIAELWRV in isoform D.		VSP_001047
	Alternative sequence	309 – 869	561	Missing in isoform D.		VSP_001048
	Alternative sequence	319 – 353	35	CSDSD…ATFNC → SLREPPCVSGNHRGGVCGLD GVRRMPTDVLFESNR in isoform C.		VSP_001045
	Alternative sequence	321 – 869	549	Missing in isoform B.		VSP_001044
	Alternative sequence	354 – 869	516	Missing in isoform C.		VSP_001046
	Alternative sequence	844 – 869	26	IVGII…HYQTI → VSEAPALPPPLREDPLARCC LCTQASHQKRRHPTRRGECG PTLALNPARLPCTRDPFPCL PADGTSVPLAVLSSQSRAST RLCLPPEMLLFTPYHWCSLV LHLRRDLRIR in isoform E.		VSP_017188
	Natural variant	198	1	G → E: dbSNP rs198400.		VAR_023051

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (Clc-6a) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: E4273777D9FF4328	FASTA	869	97,217
	10 20 30 40 50 60 MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP 70 80 90 100 110 120 YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC 130 140 150 160 170 180 SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL 190 200 210 220 230 240 LCKVLGVLFS VAGGLFVGKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRDKRD 250 260 270 280 290 300 FVSAGAAAGV AAAFGAPIGG TLFSLEEGSS FWNQGLTWKV LFCSMSATFT LNFFRSGIQF 310 320 330 340 350 360 GSWGSFQLPG LLNFGEFKCS DSDKKCHLWT AMDLGFFVVM GVIGGLLGAT FNCLNKRLAK 370 380 390 400 410 420 YRMRNVHPKP KLVRVLESLL VSLVTTVVVF VASMVLGECR QMSSSSQIGN DSFQLQVTED 430 440 450 460 470 480 VNSSIKTFFC PNDTYNDMAT LFFNPQESAI LQLFHQDGTF SPVTLALFFV LYFLLACWTY 490 500 510 520 530 540 GISVPSGLFV PSLLCGAAFG RLVANVLKSY IGLGHIYSGT FALIGAAAFL GGVVRMTISL 550 560 570 580 590 600 TVILIESTNE ITYGLPIMVT LMVAKWTGDF FNKGIYDIHV GLRGVPLLEW ETEVEMDKLR 610 620 630 640 650 660 ASDIMEPNLT YVYPHTRIQS LVSILRTTVH HAFPVVTENR GNEKEFMKGN QLISNNIKFK 670 680 690 700 710 720 KSSILTRAGE QRKRSQSMKS YPSSELRNMC DEHIASEEPA EKEDLLQQML ERRYTPYPNL 730 740 750 760 770 780 YPDQSPSEDW TMEERFRPLT FHGLILRSQL VTLLVRGVCY SESQSSASQP RLSYAEMAED 790 800 810 820 830 840 YPRYPDIHDL DLTLLNPRMI VDVTPYMNPS PFTVSPNTHV SQVFNLFRTM GLRHLPVVNA 850 860 VGEIVGIITR HNLTYEFLQA RLRQHYQTI
	Isoform B (ClC-6b) (D2-A1) [UniParc]. Checksum: 6B004FDB1915E8CA		320	35,934
	10 20 30 40 50 60 MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP 70 80 90 100 110 120 YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC 130 140 150 160 170 180 SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL 190 200 210 220 230 240 LCKVLGVLFS VAGGLFVGKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRYGKR 250 260 270 280 290 300 QERLCISRSG CWSCCSFRGA NRGYLVQSRG GFVLLEPRAH VESALLFHVC HLHPQLLPFW 310 320 DSVWKLGFLP APWIAELWRV
	Isoform C (ClC-6c) (D1-A1) [UniParc]. Checksum: 078E68BE3A147EB6		353	38,742
	10 20 30 40 50 60 MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP 70 80 90 100 110 120 YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC 130 140 150 160 170 180 SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL 190 200 210 220 230 240 LCKVLGVLFS VAGGLFVGKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRDKRD 250 260 270 280 290 300 FVSAGAAAGV AAAFGAPIGG TLFSLEEGSS FWNQGLTWKV LFCSMSATFT LNFFRSGIQF 310 320 330 340 350 GSWGSFQLPG LLNFGEFKSL REPPCVSGNH RGGVCGLDGV RRMPTDVLFE SNR
	Isoform D (ClC-6d) (D1-A2) [UniParc]. Checksum: 5BAE9FE7C2AD341E		308	34,443
	10 20 30 40 50 60 MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP 70 80 90 100 110 120 YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC 130 140 150 160 170 180 SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL 190 200 210 220 230 240 LCKVLGVLFS VAGGLFVGKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRSGCW 250 260 270 280 290 300 SCCSFRGANR GYLVQSRGGF VLLEPRAHVE SALLFHVCHL HPQLLPFWDS VWKLGFLPAP WIAELWRV
	Isoform E [UniParc]. Checksum: 1FD666515C9CA2BF		953	106,304
	10 20 30 40 50 60 MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP 70 80 90 100 110 120 YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC 130 140 150 160 170 180 SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL 190 200 210 220 230 240 LCKVLGVLFS VAGGLFVGKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRDKRD 250 260 270 280 290 300 FVSAGAAAGV AAAFGAPIGG TLFSLEEGSS FWNQGLTWKV LFCSMSATFT LNFFRSGIQF 310 320 330 340 350 360 GSWGSFQLPG LLNFGEFKCS DSDKKCHLWT AMDLGFFVVM GVIGGLLGAT FNCLNKRLAK 370 380 390 400 410 420 YRMRNVHPKP KLVRVLESLL VSLVTTVVVF VASMVLGECR QMSSSSQIGN DSFQLQVTED 430 440 450 460 470 480 VNSSIKTFFC PNDTYNDMAT LFFNPQESAI LQLFHQDGTF SPVTLALFFV LYFLLACWTY 490 500 510 520 530 540 GISVPSGLFV PSLLCGAAFG RLVANVLKSY IGLGHIYSGT FALIGAAAFL GGVVRMTISL 550 560 570 580 590 600 TVILIESTNE ITYGLPIMVT LMVAKWTGDF FNKGIYDIHV GLRGVPLLEW ETEVEMDKLR 610 620 630 640 650 660 ASDIMEPNLT YVYPHTRIQS LVSILRTTVH HAFPVVTENR GNEKEFMKGN QLISNNIKFK 670 680 690 700 710 720 KSSILTRAGE QRKRSQSMKS YPSSELRNMC DEHIASEEPA EKEDLLQQML ERRYTPYPNL 730 740 750 760 770 780 YPDQSPSEDW TMEERFRPLT FHGLILRSQL VTLLVRGVCY SESQSSASQP RLSYAEMAED 790 800 810 820 830 840 YPRYPDIHDL DLTLLNPRMI VDVTPYMNPS PFTVSPNTHV SQVFNLFRTM GLRHLPVVNA 850 860 870 880 890 900 VGEVSEAPAL PPPLREDPLA RCCLCTQASH QKRRHPTRRG ECGPTLALNP ARLPCTRDPF 910 920 930 940 950 PCLPADGTSV PLAVLSSQSR ASTRLCLPPE MLLFTPYHWC SLVLHLRRDL RIR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family." Brandt S., Jentsch T.J. FEBS Lett. 377:15-20(1995) [PubMed: 8543009] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Alternative splicing of ClC-6 (a member of the ClC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific." Eggermont J., Buyse G., Voets T., Tytgat J., De Smedt H., Droogmans G., Nilius B. Biochem. J. 325:269-276(1997) [PubMed: 9224655] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS B; C AND D), NUCLEOTIDE SEQUENCE [MRNA] OF 1-409 (ISOFORM A), TISSUE SPECIFICITY. Tissue: Chronic myeloid leukemia cell.
[3]	"Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes." Kornak U., Boesl M.R., Kubisch C. Biochim. Biophys. Acta 1447:100-106(1999) [PubMed: 10500249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
[4]	"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Bone marrow.
[5]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-198.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Brain.
[8]	"Expression of CLCN voltage-gated chloride channel genes in human blood vessels." Lamb F.S., Clayton G.H., Liu B.-X., Smith R.L., Barna T.J., Schutte B.C. J. Mol. Cell. Cardiol. 31:657-666(1999) [PubMed: 10198195] [Abstract] Cited for: TISSUE SPECIFICITY. Tissue: Aortic endothelium and Vascular smooth muscle.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X83378 mRNA. Translation: CAA58292.1. X96391 mRNA. Translation: CAA65255.1. X99472 Genomic DNA. Translation: CAA67835.1. X99473 mRNA. Translation: CAA67836.1. X99474 mRNA. Translation: CAA67837.1. X99475 mRNA. Translation: CAA67838.1. AF009257 , AF009247, AF009248, AF009249, AF009250, AF009251, AF009252, AF009253, AF009254, AF009255, AF009256 Genomic DNA. Translation: AAB69287.1. D28475 mRNA. Translation: BAA05836.4. AL953897, AL021155 Genomic DNA. Translation: CAI15891.1. AL953897, AL021155 Genomic DNA. Translation: CAI15892.1. AL953897, AL021155 Genomic DNA. Translation: CAI15893.1. AL953897, AL021155 Genomic DNA. Translation: CAI15894.1. AL953897, AL021155 Genomic DNA. Translation: CAI15895.1. AL021155, AL953897 Genomic DNA. Translation: CAI23402.1. AL021155, AL953897 Genomic DNA. Translation: CAI23403.1. AL021155, AL953897 Genomic DNA. Translation: CAI23404.1. AL021155, AL953897 Genomic DNA. Translation: CAI23405.1. AL021155, AL953897 Genomic DNA. Translation: CAI23406.1. BC117420 mRNA. Translation: AAI17421.1. BC117424 mRNA. Translation: AAI17425.1.
PIR	S68428.
RefSeq	NP_001277.1. NP_068503.1. NP_068504.1. NP_068505.1.
UniGene	Hs.193043
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P51797.
Genome annotation databases
Ensembl	ENSG00000011021. Homo sapiens. [Contig view]
GeneID	1185.
KEGG	hsa:1185.
Organism-specific databases
H-InvDB	HIX0000129.
HGNC	HGNC:2024. CLCN6.
MIM	602726. gene.
PharmGKB	PA26551.
HUGE	Search...
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P51797.
Gene expression databases
ArrayExpress	P51797.
Family and domain databases
InterPro	IPR014743. Cl-channel_core. IPR001807. Cl-channel_volt. IPR002248. Cl_channel6. IPR000644. Cysta_beta_synth_core. [Graphical view]
Gene3D	G3DSA:1.10.3080.10. Cl-channel_core. 1 hit.
PANTHER	PTHR11689. Cl-channel_volt. 1 hit.
Pfam	PF00571. CBS. 1 hit. PF00654. Voltage_CLC. 1 hit. [Graphical view]
PRINTS	PR00762. CLCHANNEL. PR01117. CLCHANNEL6.
SMART	SM00116. CBS. 2 hits. [Graphical view]
PROSITE	PS51371. CBS. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	4898.
SOURCE	Search...

Entry information

Entry name

CLCN6_HUMAN

Accession

Primary (citable) accession number: P51797
Secondary accession number(s): O60818 , O60819, O60820, O60821, P78520, P78521, Q17R81, Q5SNW2, Q5SNW3, Q5SNX1, Q5SNX2, Q5SNX3, Q99427, Q99428, Q99429

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)